The composition of the cerebrospinal fluid and brain are closely regulated by mechanisms in the central nervous system that tend to accumulate substances necessary for brain functioning as vitamins and to exclude unnecessary substances as certain drugs. This exclusion of such drugs as penicillin and gentamicin from the cerebrospinal fluid and brain makes the therapy of certain infectious diseases of the nervous system difficult. The object of this study is: 1) to gain further information about the development and function of these transport mechanisms in healthy animals as well as those with experimentally induced diseases as meningitis and uremia; and 2) to manipulate these transport mechanisms to the diseased animals' (and ultimately the patients') advantage. Particular attention will be devoted to transport processes located in the choroid plexus and to methods that will increase antibiotic concentrations in the cerebrospinal fluid. To achieve these goals, the transport of radiolabelled drugs, hormones and vitamins into and out of the cerebrospinal fluid, choroid plexus and brain, in vivo, and into the choroid plexus, in vitro, in both normal animals as well as those with experimental diseases will be documented under various conditions. BIBLIOGRAPHIC REFERENCES: Spector, R., Lorenzo, A.V. and Drum, D.E.: The binding of methyltetrahydrofolate by human serum. Biochem. Pharm. 24: 542-544, 1975. Spector, R. and Lorenzo, A.V.: Folate transport by the choroid plexus in vitro. Science 187: 540-542, 1975.